ISOPROPANOL 13-WEEK VAPOR INHALATION STUDY IN RATS AND MICE WITH NEUROTOXICITY EVALUATION IN RATS

This study was conducted to evaluate the possible subchronic toxicity as well as neurobehavioral effects of isopropanol, a widely used industrial and commercial solvent. Five groups, each containing 10 Fischer 344 rats/sex and 10 CD-1 mice/sex, were exposed for 6 hr/day, 5 days/week, for 13 weeks to isopropanel vapor at concentrations of 0 (control), 100, 500, 1500, or 5000 ppm. An additional 15 rats/sex were assigned to the 0, 500, 1500, and 5000 ppm groups for assessment of neurobehavioral function. No exposure-related mortalities occurred during the study. The narcotic effects of isopropanol were noted only during exposures at 1500 and 5000 ppm. These signs, noted during exposures, were typically absent following exposures. The only clinical signs observed following exposures included swollen periocular tissue, perinasal encrustation, and ataxia for rats of the 5000 ppm group. Neurobehavioral evaluations indicated no changes in any of the parameters of the functional observational battery; however, increased motor activity for female rats in the 5000 ppm group was noted at Weeks 9 and 13. Decreases in body weight and body weight gain were observed for rats of the 5000 ppm group at the end of the first week of exposure. During the remaining weeks, increases in body weight and/or body weight gain were observed for rats of the 1500 and 5000 ppm groups. No exposure-related effects on body weight were noted for male mice; however, increased body weight and body weight gain were observed for female mice of the 5000 ppm group. Increases or decreases in food and water consumption generally corresponded to changes in body weight and body weight gain. Various changes in clinical pathology parameters were observed for rats and female mice of the 5000 ppm group. The only organ weight effect noted was an increased relative liver weight in both sexes of rats and female mice of the 5000 ppm group. At necropsy, there were no gross lesions determined to be exposure related. Furthermore, the only microscopic change observed was hyaline droplets within the kidneys of all male rats (including controls). The size and frequency of the hyaline droplets were increased for the isopropanol exposure groups compared to the control group. These differences were not clearly concentration related, although this microscopic change was most pronounced in the high-concentration group. Neuropathologic examination revealed no exposure-related lesions in the central or peripheral nervous system of exposed rats. Thus, repeated exposures to isopropanol for 13 weeks produced toxic effects only at the highest concentration and a kidney change in male rats of unknown biological significance. (C) 1994 Society of Toxicology.